The biologic role of the mast cell has represented an enigma ever since Ehrlich discovered this cell over 100 years ago. Mast cells clearly represent an important source of inflammatory mediators in reactions of immediate (IgE-dependent) hypersensitivity. But they may also be activated during delayed hypersensitivity reactions, in the vicinity of growing tumors, and in association with a variety of other immunologic or pathologic processes in which their function is obscure. Furthermore, it has become increasingly apparent that mast cells in different anatomic sites may vary in morphology, mediator content and function, suggesting that different mast cell populations may have different roles in immunobiology or physiology. We recently showed that IL3-dependent mouse mast cell populations expressed a phenotype similar to that of one major mast cell "subtype" ("mucosal" mast cells, MMC) when grown in vitro. But when injected in vivo into congenitally mast cell-deficient WBB6F1-W/Wv mice, the adoptively transferred mast cells acquired different phenotypes in different anatomic sites: the mast cells which were detected in the stomach mucosa, a site populated by MMC in normal WBB6F1-+/+ mice, expressed features of MMC, whereas the mast cells which developed in sites ordinarily populated by "connective tissue-type" mast cells (CTMC), e.g., the skin, peritoneal cavity and stomach muscularis propria, expressed features of this mast cell "subtype." We now wish to analyze in more detail the factors regulating such "mast cell heterogeneity," using a combined in vitro and in vivo approach. In addition, we wish to develop further and exploit our new model system for analyzing the role of different mast cell populations in immunobiology: congenitally mast cell-deficient WBB6F1-W/Wv mice whose mast cell populations have been selectively restored by transplantation of WBB6F1-+/+ mast cells grown in vitro. By testing these mice at different intervals after transplantation (e.g., at early intervals, when skin and peritoneal mast cells exhibit the "MMC" phenotype, and at late intervals, when the cells have acquired the "CTMC" phenotype), we will be able to determine whether mast cell populations at different stages of maturation/differentiation express differences in function.